Respiration2 upload

Spirogram

Volumes & Capacities

• Tidal volume x frequency of breaths = Total ventilation (L/min)

Factors affecting Vol & Capacities

• Inspiratory reserve volume (IRV)• Current lung volume• Lung compliance• Muscle strength• Comfort• Flexibility of skeleton• Posture

• Expiratory reserve volume (ERV)• Same as above + strength of abdominal M

Why have RV?

• Airways would collapse– Would take an unusually high pressure to inflate

them during inspiration– Modest RV minimizes airway collapse, thereby optimizing

ventilation efficiency

– Would affect blood oxygenation– Blood flow to the lungs and other parts of the body is

continuous– During collapse – Po2 will plummet

Expiratory Flow• Spirometry yields

FVC in 2 ways:– Spirogram (Volume-

time)• Provides*:

– FVC– FEV1

– FEV1/FVC– **FEF25-75 (also called

MMEF***)

– Flow-volume loop

Normal Values

• FVC = 5.0 L• FEV1 = 3.8 L

• FEF25-75 = 3.25 L/sec

• FEV1/FVC = 0.76• PEFR = 10 L/sec

FEV1

• Volume of air that can expired in the 1st second of a forced maximal expiration– Normally 80% of vital capacity, expressed as:

• FEV1/VC = 0.8

– Obstructive lung disease (asthma) – FEV1 is reduced more than VC (FEV1/VC decreased)

– Restrictive lung disease (fibrosis) – both FEV1 & VC are reduced (FEV1/VC normal or increased – since their elastic recoil is more aggressive!)

Helium Dilution Method(for TLC & FRC)*

– [He]initial = 10%

– VS(initial) = 2 L

– [He]final = 5% (assume)

– Final Vol = VS + VL

• C1xV1 = C2xV2• [He]initial x VS= [He]final

x (VS +VL)

Dead Space

• Volume that does not participate in gas exchange

• Anatomical & Physiological

• Anatomical DS• Nose (and/or mouth), trachea, bronchi, and

bronchioles• Volume = 150 ml

– Hence out of VT only 350 ml reaches gas exchange areas– First air expired – DS air – To sample alveolar air - sample end-expiratory air

Dead Space

Anatomical DS: Fowler’s Method

Assuming:Gray area: 30 sq. cm Pink area is 70 sq. cmTotal volume expired = 500 mlDS would be:

Physiological DS: Bohr’s Method

• Based on:– Measurement of PCO2 of mixed expired air (PECO2) AND– 3 assumptions:

(1) All of CO2 in expired air comes from exchange of CO2 in functioning (V & Q) alveoli; (2) There is no CO2 in inspired air

(3) Physiologic DS neither exchanges nor contributes any CO2

• If Physiologic DS = 0 then,– PECO2 = alveolar PCO2

• If Physiologic DS = x then,– PECO2 < alveolar PCO2

» Diluted by physiologic DS

Physiological DS: Bohr’s Method

• Hence, by comparing PECO2 with PACO2, dilution factor can be measured

• This dilution factor reflects Physiologic DS

• Problem: alveolar air cannot be sampled directly

• Solution: arterial PACO2 (PaCO2)reflects alveolar PACO2

– Fraction is dilution factor

Ventilation Rates• Volume of air moved into & out of lungs per

unit time• Ventilation rate can be expressed in 2 ways:

• Minute ventilation– Total rate of air movement into & out of lungs/minute– VT x breathes/min = 500 x 12 = 6L/min

• Alveolar ventilation– Total rate of air movement into & out of lungs/minute

(corrected for DS)– (VT – VD) x breathes/min

– (500 – 150) x 12 = 4200 ml/min

Example: Calculating Ventilation Rates

• A man who has the following data: – Tidal volume = 550 mL – Breathing rate = 14 breaths/min– PCO2 (arterial blood) = 40 mm Hg

– PCO2 (expired air) = 30 mm Hg.

• What is his minute ventilation? • What is his alveolar ventilation? • What percentage of each tidal volume reaches functioning

alveoli? • What percentage of each tidal volume is dead space?

Alveolar Ventilation Equation

• Fundamental relationship of respiratory physiology

• Describes the inverse relationship b/w VA & alveolar PCO2 (PACO2)

• or

Effect of Variations in Respiratory Rate and Depth of Alveolar Ventilation

Respiratory rate 30/min 10/min

Tidal volume 200 mL 600 mL

Minute volume 6 L 6 L

Alveolar ventilation (200 – 150) x 30 = 1500 mL

(600 – 150) x 10 = 4500 mL

Pulmonary Circulation (Perfusion)

Pulmonary Circulation• Pulmonary artery (differences from systemic

arteries)– Thinner– Larger in diameter– Highly distensible– Less no. of arterioles– Overall VERY COMPLIANT (7 ml/mm Hg = entire systemic arterial tree!)

» Accommodate 2/3 of SV of right ventricle

• Pulmonary veins– As distensible as systemic veins

• Bronchial vessels– 1-2 % of total C.O.– Oxygenated blood– Supplies lung tissue– Bronchial veins empty into the left atrium– Bronchial (& coronary) vessels causing slight shunting of blood

» Physiological shunt (PO2 of arterial blood is 2 mm Hg < than pulmonary vein blood)

Pulmonary Circulation

• Pressures in pulmonary system• Right ventricle

– Systolic 25 mm Hg– Diastolic 0-1 mm Hg

• Pulmonary artery– Systolic 25 mm Hg– Diastolic 8 mm Hg– Mean 15 mm Hg

• Pulmonary arteriolar P (mean) – 12 mm Hg• Pulmonary capillary P (mean) – 10.5 mm Hg• Pulmonary venous P (mean) – 9 mmHg

Pulmonary Circulation

• Left atrial P & pulmonary venous P– Mean P in left atrium and major pulmonary veins – 2 mm

Hg (recumbent)– Pulmonary Wedge Pressure

– 5 mm Hg– Role in estimating pulmonary capillary P & left atrial P

• Blood flow through the lungs and its distribution• Blood flow through lungs = C.O.• Poorly aerated areas – vasoconstriction

– Diversion of blood to better aerated areas– Time spent by RBC in navigating pulmonary capillary – 0.75 sec (total

amount 75 ml)» During exercise – 200 ml with time shortened

Distribution of Pulmonary Blood Flow

• Pulmonary circ. is low pressure/low resistance

• Hence gravity affects it more– This effect causes ‘uneven’ perfusion in

lungs– Blood flow increases from apex to base

(upright posture)– Recumbent posture: flow > in posterior than

anterior– Supine: flow equalizes

• In stress (excercise)– All areas even out!


• Hydrostatic Pressure (HP) difference in lungs

• Difference between highest & lowest point in lung – 30 cm apart

• This causes a pressure gradient of 23 mmHg– 15 mmHg above heart

level– 8 mmHg below heart level

• Another way to look at it:• Every 1 cm that an artery

has to ‘ascend’ the lung– A change in HP of 0.74

mmHg (1 cm H2O) occurs

• So an ‘ascend’ of 10 cm above heart level– Induces HP change of 7.4

mmHg

• HP at heart level = 14 mmHg– So, 14 <minus> 7.4 = 6.6

mmHg (arterial P in upper areas)


• Gravity affects arteries & veins alike throughout lung fields

• This also affects ventilation (V/Q ratios)• Meaning, perfusion affects ventilation

• Conversely, alveolar pressure also influences perfusion

• Meaning, ventilation affects perfusion


• PA = pulmonary alveolar pressure

• Pa = pulmonary arterial pressure

• PV = pulmonary venous pressure

Lung Zones• Zone 1

– No blood flow during any part of cardiac cycle• PA > Pa > PV• Occurs in abnormalities such as:

– Positive pressure ventilation (Palv >>>)– Hemorrhage (Ppc <<<)

• Zone 2– Pa > PA > PV

• Going down into zone 2– Hydrostatic P increases increasing Pa

• Zone 3– Pa > PV > PA

• Normally,– Zone 2 present in 10 cm above heart level to upper lung areas– Zone 3 present in 10 cm above heart level to lower lung areas– During exercise – entire lung may become – Zone 3!

• In vivo• During respiratory cycle:

– PA b/c –ve during inspiration (promoting dilation of capillaries)– During expiration it becomes +ve (constricting capillaries)

• During cardiac cycle• P in arterioles & capillaries is >>> during systole

» Thus promoting dilation of pulmonary capillaries• And is lowest during diastole

» Thus promoting dilation of pulmonary capillaries

• Thus blood flow through an alveolar vessel would be greatest when inspiration coincides with systole!!

Ventilation-Perfusion Ratio (V/Q)

• Defined as ratio of ventilation to blood flow• Can be defined for:

• Single alveolus (VA / capillary flow)• Group of alveoli• Entire lung (Total VA / C.O.)

• Normal lung• Overall V/Q = 0.8

– Total VA = 4 L/min, CO = 5 L/min

• This value is averaged – differs in various zones


• V/Q only describes the nature of relationship b/w V & Q

• So a normal V/Q only means the relation is normal*

Integrating Lung Zones & V/Q Concept

• V & Q are both gravity-dependent; both increase down the lung

• Q shows about a 5-fold difference b/w the top & bottom of lung

• V shows about a 2-fold difference– This causes gravity-dependent regional

variations in the V/Q – Ranging from 0.6 (base) - 3 or higher

(apex)

• Q is proportionately greater than V at the base, and

• V is proportionately greater than Q at the apex

V/Q Affects Gas Exchange

• Three scenarios• Va/Q = 0

– Alveolar air equilibrates with venous blood

• Va/Q = infinity– Alveolar air

equilibrates with inspired air

• Va/Q = normal


• Physiological Shunt (V/Q= less than normal)• Some blood may not get oxygenated due to poorly ventilated

alveoli – shunted blood• This, along with bronchial & coronary blood – Physiological Shunt• Measurement:

– analyzing the concentration of O2 in both mixed venous blood and arterial blood, along with simultaneous measurement of cardiac output.

• Greater the physiologic shunt - greater the amount of blood that fails to be oxygenated!


• Physiological Dead Space (V/Q= greater than normal)– Ventilation ‘wasted’– Ventilation is also wasted in anatomical DS– Together : Physiological DS– Measurement:

• appropriate blood and expiratory gas measurements into the following:

• When the physiologic dead space is great - much of thework of ventilation is wasted

Abnormalities of V/Q ratio

• Abnormal V/Q - Upper and Lower in Normal Lung

• Normal person – upright position– Lung upper regions: Va/Q higher (Physio. DS)– Lung lower regions: Va/Q lower (Physio. Shunt)

• In both cases – lung’s effectiveness for gas exchange decreases• In exercise – situation improves!

Abnormalities of V/Q ratio

• Abnormal V/Q in COPD– various degrees of bronchial obstruction occurs– Emphysema occurs resulting in 2 scenarios:

• Small bronchioles obstructed – alveoli unventilated – V/Q = 0

• Other areas – wall destruction causes loss of blood vessels – ventilation wasted – V/Q = infinity

Alveolar-Arterial Difference (AaDO2)

• Relationship b/w PAO2 and PaO2

– Even in normal people – there is a slight difference b/w the two

– Difference is called AaDO2

• This slight difference is caused bu mixing of venous blood (thebesian + broncial veins) into oxygenated blood

– Increased AaDO2 is indicative of impaired gas exchange

GAS TRANSPORT

Pulmonary Capillary Dynamics

Pulmonary Edema

• Any factor – causing pulmonary interstitial fluid pressure to rise from : -ve to +ve

• Left-sided heart failure or mitral valve disease• Damage to the pulmonary blood capillary

membranes caused by infections (pneumonia) or noxious material• Pulmonary Edema Safety Factor

– Pulmonary Capillary Pressure must rise - 7 mm Hg to > 28 mm Hg to cause pulmonary edema

– This provides an acute safety factor against pulmonary edema of 21 mm Hg

Respiratory Membrane

• Respiratory Unit (also called “respiratory lobule”) – Composed of:• Respiratory bronchiole • Alveolar ducts • Atria• Alveoli

Respiratory Membrane

Forms of Gases in Solution

• In alveolar air:• There is one form of gas (expressed as a partial

pressure)

• In solutions (blood):• Gases are carried in additional forms:

– Gas may be dissolved– It may be bound to proteins– It may be chemically modified.

» Hence total gas concentration in solution= dissolved gas + bound gas + chemically modified gas

• Partial pressure of gas in a solution is exerted only by dissolved form!!

Gas Transfer & Transport

• Two types of gas movements in lungs• Bulk flow (trachea to alveoli)• Diffusion (alveoli to blood)

• Henry law states• At equilibrium, amount of gas dissolved in a liquid (at a given

temperature) is directly proportional to parital P & solubility of a gas

• Fick law states• Volume of gas diffusing per minute across a membrane is directly

proportional to:» membrane surface area» diffusion coefficient of the gas » partial pressure difference of the gas

• And is inversely proportional to membrane thickness

Capillary blood flow & gas uptake

• Perfusion-limited vs Diffusion-limited gases*– Difference b/w N2O, O2 and CO

O2 Transport in Blood

• O2 is carried in 2 forms in blood: • Dissolved• Bound to Hb

– Dissolved form• Free in solution • Approx. 2% of total O2 content of blood

• The only form of O2 that produces a partial pressure

• At normal PaO2 = 100 mm Hg, – Concentration of dissolved O2 = 0.3 mL O2/100 mL– Insufficient to meet tissue demands*

– Bound with Hb• Remaining 98% of the total O2 content of blood is

reversibly bound to Hb– Hemoglobin

» Globular protein consisting of four subunits» Each subunit can bind one molecule of O2 - total of four

molecules of O2 per molecule of Hb

» For the subunits to bind O2, iron in the heme moieties must be in the ferrous state (i.e., Fe2+)

O2-binding Capacity, O2 Content & O2 Saturation

• O2-binding capacity – max. amount of O2 that can be bound to Hb per volume of blood

» 1 g Hb = 1.34 mL O2 » Normal conc. of Hb = 15 g/100 mL» O2-binding capacity of Hb= 20.1 mL O2/100 mL blood

• O2 content - actual amount of O2 per volume of blood

Problem

• An arterial blood gas reveals:• PaO2 = 60 mmHg

• O2 saturation (SaO2) = 90%• Patient's Hb = 14 g/dl

• What is the total (Hgb-bound +dissolved) O2 content?

– O2 content = (14gm/dl x 1.34) x 90/100 + 0.3ml/dl– O2 content = 17.18 ml/dl– (normal = 20 ml/dl)

– The patient is treated with 30% supplemental O2, and a repeat arterial blood gas reveals:• PaO2 of 95 mmHg

• O2 saturation of 97%

• What is the total O2 content now? • 18.49


• Quaternary structure of Hb determines its O2 affinity:

– T (tense) configuration: Hb in deoxygenated blood– R (relaxed) configuration: Hb in oxygenated blood– R state has 500-fold more affinity for O2 than T state– Positive cooperativity


• Hb – O2 Dissociation Curve– Studies the relation between PO2 and hemoglobin % saturation or O2

content of blood (O2 volume %)

– At arterial PO2 = 95 mmHg (resting conditions)

» Hb % saturation = 97%» O2 volume % = 19.4 ml (~ 20 ml)

– At venous PO2 = 40 mmHg (resting conditions)

» Hb % saturation = 75 %» O2 volume % = 14.4 ml

– P50 – partial pressure of O2 at which ½ Hb is saturated

• Basis of shape of the curve being sigmoid– Positive cooperativity

Hb – O2 Dissociation Curve

• Maximum amount of O2 that can combine with Hb– Normal conc. of Hb in blood = 15 gms/dl– 1 gm Hb can bind = 1.34 ml O2

– 15 gm Hb can bind = 19.4 ml O2 (~20 volume %)

• In other words every 100 ml (dl) delivers ~ 20 ml of O2

• Amount of O2 released from Hb to tissues • Arterial blood status

» PO2: 95 mmHg

» Hb% saturation: 97%» O2: 19.4 volume %

• Venous blood status» PO2: 40 mmHg

» Hb% saturation: 75%» O2: 14.4 volume %

Hb – Tissue Oxygen Buffer

• ‘Based on tissue need’– Under basal conditions

– Tissue O2 requirements = 5 ml/dl

– Change in Po2 = 55 mmHg

– O2 release = 5 ml/dl

– Under heavy exercise– Extra 15-25 mmHg change

in Po2 achieves – large release of O2 to tissues

– Reason: Po2 < 40 mmHg lies on STEEP part of curve – LESS change in Po2 results in MORE O2 release

Hb – Tissue Oxygen Buffer

• ‘Buffering action at fluctuating Alveolar Po2’• Alveolar Po2 fluctuates:

» At high altitudes: alveolar Po2 DECREASES

» In deep sea: alveolar Po2 INCREASES

• If alveolar Po2 falls to 60 mmHg – » Blood Hb% - 89% (only 8% less than max. saturation)» Hb%= 89 (5 ml O2 taken away – resting Po2 in venous blood 35

mmHg)

• If alveolar Po2 rises to 500 mmHg – » Blood Hb% - 100% (only 3% above max. saturation)» Hb%= 100 (5 ml O2 taken away – resting Po2 in venous blood is

only slightly higher)

Shift of Hb – O2 Dissociation Curve

– Temperature• Increase – right shift• Decrease – left shift• High temperature decreases Hb affinity

for O2– Excercising muscle!– Skin in cold temperature!

– 2,3-DPG• @ rest – right shift in systemic

circulation (beneficial)• May cause difficulty in O2 pickup in

lungs (if conc. Increases)– Exercise

• Right shift

Shift of Hb – O2 Dissociation Curve

– Acid (Bohr pH effect)• Metabolically active tissues – H+ production – displaces

O2 from incoming Hb – Right shift• Lungs – increased Po2 – displaces H+ - left shift

– CO2 (Bohr CO2 effect)• Hypercapnia in tissues – right shift

– CO poisoning, HB-F• Left shift

CO Poisoning • Hb binding site for O2 and CO is the same!• Binding capability of CO with Hb is 250 folds more than O2

• Alveolar pressure of 0.4 mmHg (1/250 of normal Po2) • CO competes equally with O2 for hemoglobin• causes 1/2 Hb to bind with CO instead of with O2

• Alveolar pressure of 0.6 mmHg – Lethal• Clinical scenario

• Patient comes in with nervous signs • No obvious signs of hypoxemia (no cyanosis, bright red blood,)• Po2 is normal – body does not detect hypoxia!

• Treatment• Pure O2 with 5% CO2

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